| Chronic inflammatory bone diseases, such as rheumatoid
arthritis, periodontal disease and aseptic periprosthetic osteolysis, are
characterized by bone loss around affected joints and teeth caused by increased
osteoclastic bone resorption. This resorption is mediated largely by the
increased local production of pro-inflammatory cytokines, such as tumor
necrosis factor-alpha (TNFα). These cytokines may induce resorption indirectly
by affecting the production of the essential osteoclast differentiation
factor, receptor activator of NF-kB ligand, and/or its soluble decoy receptor,
osteoprotegerin, by osteoblast/stromal cells or directly by enhancing proliferation
and/or activity of cells in the osteoclast lineage. The importance of TNFα
in the pathogenesis of various forms of bone loss is supported by both experimental
and clinical evidence. However, TNFα is not absolutely required for osteoclastogenesis,
erosive arthritis, or osteolysis, as all these events could occur in the
absence of TNFα and whether TNFα promotes osteoclast formation independently
of RANK signaling is still a topic of debate. Here we review our current
understanding of the mechanisms whereby TNFα increases osteoclastogenesis
in vitro and in vivo. |
